Abstract [en]

Micro-structurally based models for smooth muscle contraction are crucial for a better understanding of pathological conditions such as atherosclerosis, incontinence and asthma. It is meaningful that models consider the underlying mechanical structure and the biochemical activation. Hence, a simple mechanochemical model is proposed that includes the dispersion of the orientation of smooth muscle myofilaments and that is capable to capture available experimental data on smooth muscle contraction. This allows a refined study of the effects of myofilament dispersion on the smooth muscle contraction. A classical biochemical model is used to describe the cross-bridge interactions with the thin filament in smooth muscles in which calcium-dependent myosin phosphorylation is the only regulatory mechanism. A novel mechanical model considers the dispersion of the contractile fiber orientations in smooth muscle cells by means of a strain-energy function in terms of one dispersion parameter. All model parameters have a biophysical meaning and may be estimated through comparisons with experimental data. The contraction of the middle layer of a carotid artery is studied numerically. Using a tube the relationships between the internal pressure and the stretches are investigated as functions of the dispersion parameter, which implies a strong influence of the orientation of smooth muscle myofilaments on the contraction response. It is straightforward to implement this model in a finite element code to better analyze more complex boundary-value problems.

Murtada, Sae-Il

KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).

2012 (English)Doctoral thesis, comprehensive summary (Other academic)

Abstract [en]

Smooth muscle has an important role in several physiological processes, where it regulates the wall tension and the size of hollow organs. In blood vessels, the contraction and relaxation of smooth muscle contribute to the mechanical stability of the vessel wall and determines the diameter. To better understand how the active tone of smooth muscle influences the passive layers of the artery wall and how dysfunctions of the smooth muscle are related to pathologies such as hypertension and vasospasm, a coupled chemomechanical model based on structural studies and contractile behavior was proposed in this thesis. Smooth muscle contraction arises when cross-bridges between the myosin and actin filament cycle, causing sliding of the filaments. The contraction is triggered when myosin is phosphorylated by an influx of intracellular calcium ions, which can be initiated through different excitation-contraction pathways.

The proposed model coupled a chemical model, where intracellular calcium ion concentration was related to myosin phosphorylation and the fraction of load-bearing cross-bridges, with a mechanical model which was based on the three-element Hill model. The mechanical model, which described a sarcomeric equivalent contractile unit based on structural observations had been developed and modified in different steps to capture the characteristics of smooth muscle behavior, such as isometric contraction, isotonic shortening velocities and length-tension relationships. The chemical material parameters were fitted to calcium-phosphorylation data found in the literature and the mechanical model was fitted against experiments on swine common carotid media performed at Karolinska Instititet, Stockholm. The final coupled model was implemented into a three-dimensional finite element code to simulate the active tone in a two layered artery exposed to realistic pressure pulses. Simulation results indicated that changes in intracellular calcium amplitudes did not have significant effects while changes in the mean value of the intracellular calcium and in the medial wall thickness had a more significant effect on the mechanical response of the arterial wall.